Hypertonic mannitol solutions are used clinically for:
The hypertonicity causes passive movement of water across lipid barriers in response to the osmotic gradient.
Mannitol is a monosaccharide which is easy to produce and stable in solution. It is used clinically in doses ranging from 0.25 to 1.5 g/kg body weight. Solutions of 10% and 20% mannitol are readily clinically available.
Mannitol does not cross the blood brain barrier so an elevated plasma osmolality due to a infusion of hypertonic mannitol is effective in removing fluid from the brain. This is called 'mannitol osmotherapy'. In the past other hypertonic solutions (eg hypertonic urea solution) have been used and currently in some places hypertonic glycerol solutions are available as an alternative to mannitol.
Mannitol infusions are useful to acutely decrease elevated intracranial pressure due to an intracranial space occupying lesion. A typical use would be in a patient with an intracerebral haematoma due to an acute traumatic head injury. The effect is rapid in onset (minutes) but only temporary (as the mannitol is excreted) but its use buys time for urgent definitive therapy (eg surgical evacuation of the haematoma and surgical haemostasis). A typical dose in an adult would be 0.5-1.5g/kg administered as the 20% solution.
Repeated doses of mannitol have less effect and as some slowly enters the brain, rebound intracranial hypertension is a risk. As the blood-brain barrier is probably disrupted in damaged areas of the brain, mannitol may be both less effective here and also more may enter the brain at these places. However, the therapeutic effect of mannitol is not dependent on a specific action at damaged areas of the brain but rather on a global effect in decreasing intracranial fluid volume and intracranial pressure so this has little relevance for a first dose of mannitol and especially if definitive surgical treatment is successful. Much more problematical is use of repeated doses of mannitol in ICU patients with traumatic intracranial hypertension in whom there is no surgically correctable cause; such use is usually futile.
The brain cells also compensate for the presence of continued hypertonicity by the intracellular production of 'idiogenic osmoles'. The effect is to increase intracellular tonicity and allow brain cell volume to return towards normal presumably with improvement of intracellular functions despite the continued hypertonicity.
Use of mannitol infusions is common intraoperatively in some neurosurgical procedures. The aim is to decrease intracranial pressure and produce a 'slack brain' to facilitate surgical access.
Mannitol does not cross cell membranes so the cell volume of most other cells in the body is also decreased.
In the renal glomeruli, mannitol is freely filtered. It is not secreted or reabsorbed by the tubules. In the doses used clinically it retains water with it in the tubule and causes an 'osmotic diuresis'. Consequently, mannitol is classified as an 'osmotic diuretic'. The high flow of retained tubule fluid tends to have a flushing effect and washes fluid and solutes from the kidney. This effect is useful clinically in management of rhabdomyolysis. The aim is to 'wash' the myoglobin out of the tubules and prevent it precipitating there with obstruction and development of acute renal failure. The effect of mannitol for this use is aided by maintenance of adequate intravascular volume and by urinary alkalinisation (by administration of IV sodium bicarbonate).
Attention to intravascular volume status is important during any clinical use of mannitol. Initially, the tissue dehydrating effect will increase intravascular volume with the risk of precipitating volume overload and hypertension and/or acute congestive heart failure. Subsequently, the diuretic effect may result in hypovolaemia (and hypernatraemia). Frusemide (a loop diuretic) may be a useful adjunct in some cases to minimise the initial hypervolaemia.
The increased intravascular water volume decreases the red cell concentration (decreased haematocrit) with a resultant decrease in blood viscosity. This may improve flow and oxygen delivery to some areas.
Mannitol has free radical scavenging properties and these may contribute to its therapeutic effects (though this has not so far been established).